Pharmacological properties
Pharmacodynamics. Acetylsalicylic acid is an analgesic, anti-inflammatory, antipyretic and antiplatelet agent. Antiaggregatory properties increase bleeding time.
The main pharmacological effect is inhibition of the formation of prostaglandins and thromboxanes. The analgesic effect is additional, which is due to inhibition of the COX enzyme. The anti-inflammatory property is associated with a decrease in blood flow caused by inhibition of the synthesis of PGE 2.
Acetylsalicylic acid irreversibly inhibits the synthesis of prostaglandins G / H, its effect on platelets is longer than its presence in the body. The effect of acetylsalicylic acid on the biosynthesis of thromboxane in platelets and on bleeding time continues for a long time after discontinuation of treatment. The effect ceases only after the appearance of new platelets in the blood plasma.
Salicylic acid (the active metabolite of acetylsalicylic acid) has an anti-inflammatory effect and also affects respiratory processes, acid-base balance and gastric mucosa. Salicylates stimulate respiration, mainly by exerting a direct effect on the bone marrow. Salicylates exert an indirect effect on the gastric mucosa by inhibiting its vasodilator and cytoprotective prostaglandins and increase the risk of ulcers.
Pharmacokinetics. Absorption. After oral administration, acetylsalicylic acid is rapidly absorbed from the gastrointestinal tract. After oral administration, the absorption of the non-ionized form of acetylsalicylic acid occurs in the stomach and intestines. The rate of absorption is reduced by food intake and in patients with migraine attacks, and increases in patients with achlorhydria or in patients taking polysorbates or antacids. C max in serum is reached after 1-2 hours.
Distribution. The binding of acetylsalicylic acid to plasma proteins is 80-90%. The volume of distribution for adults is 170 ml/kg body weight. With increasing plasma concentration, saturation of the active sites of proteins occurs, which leads to an increase in the volume of distribution. Salicylates are extensively bound to plasma proteins and are rapidly distributed throughout the body. Salicylates penetrate into breast milk and can penetrate the placental barrier.
Metabolism. Acetylsalicylic acid is hydrolyzed to the active metabolite - salicylic acid in the stomach wall. After absorption, acetylsalicylic acid is rapidly converted to salicylic acid, but during the first 20 minutes after ingestion it is dominant in the blood plasma.
Excretion. Salicylic acid is metabolized mainly in the liver. Thus, the equilibrium concentration of salicylate in the blood plasma increases disproportionately to the dose taken. At a dose of 325 mg, the elimination of acetylsalicylic acid occurs with the participation of first-order reaction kinetics. T ½ is 2-3 hours. At a high dose of acetylsalicylic acid, T ½ increases to 15-30 hours. Salicylic acid is also excreted unchanged in the urine. The volume excreted depends on the dose level and urine pH. About 30% of salicylic acid is excreted in the urine if the urine reaction is alkaline, only 2% - with an acidic reaction. Excretion by the kidneys occurs due to the processes of filtration, active secretion of the renal tubules and passive tubular reabsorption.
Indication
Cardiomagnyl
Acute and chronic ischemic heart disease; prevention of re-thrombosis; primary prevention of thrombosis, cardiovascular diseases, such as acute coronary syndrome in patients over 50 years of age in the presence of risk factors for the development of cardiovascular diseases: arterial hypertension, hypercholesterolemia, diabetes mellitus, obesity (body mass index 30), hereditary anamnesis (myocardial infarction in patients under 55 years of age in at least one parent or brother or sister);
Cardiomagnyl Forte
Acute and chronic ischemic heart disease.
Application
Cardiomagnyl
Acute and chronic ischemic heart disease: recommended initial dose - 150 mg/day. Maintenance dose - 75 mg/day.
Acute myocardial infarction. Unstable angina: the recommended dose is 150-450 mg, administered as early as possible after the onset of symptoms.
Prevention of recurrent thrombosis: the recommended initial dose is 150 mg/day. Maintenance dose is 75 mg/day.
Primary prevention of thrombosis, cardiovascular diseases such as acute coronary syndrome in patients with risk factors for cardiovascular diseases. The recommended preventive dose is 75 mg/day.
Cardiomagnyl Forte. The recommended dose for adults is 150 mg (1 tablet) per day.
The tablets are swallowed whole with water. To ensure rapid absorption, the tablet can be chewed or dissolved in water.
Hepatic impairment. The drug is not used in patients with severe hepatic impairment. Dose adjustment may be necessary in patients with hepatic impairment.
Renal impairment. The drug is not used to treat patients with severe renal insufficiency (glomerular filtration rate 0.2 ml / s (10 ml / min)). Dose adjustment may be required in patients with impaired renal function.
Hypersensitivity to acetylsalicylic acid, other salicylates or any component of the drug; asthma caused by the use of salicylates or substances with a similar effect, especially non-steroidal anti-inflammatory drugs in history; acute ulcer; hemorrhagic diathesis; severe renal failure; severe hepatic failure; severe heart failure; combination with methotrexate at a dose of ≥15 mg/week (see interactions).
Side effects
The information on adverse reactions provided is based on spontaneous post-marketing reports of adverse reactions with all dosage forms and strengths of acetylsalicylic acid (including oral administration during short and long-term treatment). However, classification of adverse reactions into CIOMS III frequency categories has not been performed.
Gastrointestinal disorders: frequent signs and symptoms of dyspepsia, epigastric pain and abdominal pain; in isolated cases - inflammation of the gastrointestinal tract, erosive-ulcerative lesions of the gastrointestinal tract, which can in isolated cases lead to gastrointestinal hemorrhage and perforation with corresponding laboratory parameters and clinical manifestations.
Due to its antiplatelet effect on platelets, acetylsalicylic acid may be associated with a risk of bleeding and prolongation of bleeding time. Bleeding events such as PERIOPERATIVE hemorrhages, hematomas, urogenital bleeding, epistaxis, and gingival bleeding have been reported; rarely or very rarely, serious bleeding events such as gastrointestinal hemorrhages and cerebral hemorrhages (especially in patients with uncontrolled hypertension and/or concomitant use of antihemostatic agents), which in some cases could be potentially life-threatening. Bleeding events may lead to acute and chronic posthemorrhagic anemia/iron deficiency anemia (due to so-called occult microbleeding) with associated laboratory and clinical signs such as asthenia, pallor of the skin, and hypoperfusion.
Hemolysis and hemolytic anemia have been reported in patients with severe forms of glucose-6-phosphate dehydrogenase deficiency.
Renal impairment and acute renal failure have been reported. Hypersensitivity reactions with associated laboratory and clinical manifestations, including asthmatic status, mild to moderate skin reactions, and respiratory, gastrointestinal and cardiovascular reactions, including symptoms such as rash, urticaria, oedema, pruritus, rhinitis, nasal congestion, cardiorespiratory failure and very rarely severe reactions, including anaphylactic shock.
Very rarely, transient hepatic failure with increased serum transaminases and LF levels has been reported.
Dizziness and ringing in the ears have been reported, which may indicate an overdose.
Special instructions
The drug Cardiomagnyl / Cardiomagnyl forte is used with caution in the following situations:
hypersensitivity to analgesics, anti-inflammatory, antirheumatic drugs, as well as in the presence of allergies to other substances; gastrointestinal ulcers, including chronic and recurrent peptic ulcer disease or gastrointestinal bleeding in history; simultaneous use of anticoagulants; in patients with impaired renal function or patients with circulatory disorders (for example, renal vascular pathology, congestive cardiovascular failure, hypovolemia, major surgery, sepsis or severe bleeding), since acetylsalicylic acid may also increase the risk of impaired renal function and acute renal failure; in patients with severe glucose-6-phosphate dehydrogenase deficiency, acetylsalicylic acid may cause hemolysis or hemolytic anemia. Especially in the presence of factors that may increase the risk of hemolysis, such as high doses of the drug, fever or acute infectious process; impaired liver function.
Ibuprofen may reduce the inhibitory effect of acetylsalicylic acid on platelet aggregation. In the case of using the drug Cardiomagnyl / Cardiomagnyl Forte, the patient should consult a doctor before starting to take ibuprofen as an analgesic. Acetylsalicylic acid may cause the development of bronchospasm or an asthma attack or other hypersensitivity reactions. Risk factors include a history of asthma, hay fever, nasal polyps or chronic respiratory disease, allergic reactions (e.g. skin reactions, itching, urticaria) to other substances in history.
When using acetylsalicylic acid in low doses, the excretion of uric acid may decrease. This may lead to an attack of gout in predisposed patients. Do not use drugs containing acetylsalicylic acid in children and adolescents with acute respiratory viral infections, with or without fever, without consulting a doctor. With some viral diseases, especially influenza A, influenza B and chickenpox, there is a risk of developing Reye's syndrome, which is a very rare but life-threatening disease and requires urgent medical intervention. The risk may be increased if acetylsalicylic acid is used as a concomitant drug, but a causal relationship in this case has not been proven. If these conditions are accompanied by persistent vomiting, this may be a manifestation of Reye's syndrome.
Use during pregnancy and breastfeeding. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Available epidemiological data indicate a risk of miscarriage and foetal malformations after use of prostaglandin synthesis inhibitors in early pregnancy. The risk increases with increasing dose and duration of therapy. According to the available data, the association between acetylsalicylic acid and an increased risk of miscarriage has not been confirmed.
The available epidemiological data on the occurrence of malformations are not consistent, but an increased risk of gastroschisis cannot be excluded with the use of acetylsalicylic acid. The results of a prospective study of exposure in early pregnancy (1-4 months) involving approximately 14,800 mother-child pairs do not indicate any association with an increased risk of malformations. Animal studies indicate reproductive toxicity.
In the first and second trimesters of pregnancy, drugs containing acetylsalicylic acid should not be prescribed unless clearly necessary. In women who may be pregnant or in the first and second trimesters of pregnancy, the dose of drugs containing acetylsalicylic acid should be as low as possible and the duration of treatment as short as possible.
In the third trimester of pregnancy, all prostaglandin synthesis inhibitors can affect the fetus in the following ways:
Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction with possible further development of renal failure with oligohydramnios.
Prostaglandin synthesis inhibitors can affect a woman and her baby in the following ways at the end of pregnancy:
the possibility of prolonging bleeding time, an antiplatelet effect that may occur even after using the drug in very low doses; inhibition of uterine contractions, which may lead to a delay or increase in the duration of labor.
Given this, acetylsalicylic acid is contraindicated in the third trimester of pregnancy.
Salicylates and their metabolites pass into breast milk in small quantities. Since no harmful effects on the child have been observed after administration to nursing mothers, interruption of breastfeeding is usually not necessary. However, in cases of regular use or when using the drug in high doses, breastfeeding should be discontinued early.
Children. According to the indications (see Method of administration), the drug Cardiomagnyl / Cardiomagnyl Forte is not used in children.
The use of acetylsalicylic acid in children under 15 years of age can cause severe side effects (including Reye's syndrome, one of the signs of which is constant vomiting).
The ability to influence the reaction speed when driving vehicles or other mechanisms. Does not affect.
Interactions
Contraindications for concomitant use
Methotrexate. The use of acetylsalicylic acid and methotrexate at a dose of ≥15 mg/week increases the hematological toxicity of methotrexate (reduction in renal clearance of methotrexate by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates).
ACE inhibitors in combination with acetylsalicylic acid in high doses cause a decrease in glomerular filtration due to inhibition of the vasodilator effect of prostaglandins and a decrease in the antihypertensive effect.
Acetazolamide: Possible increase in acetazolamide concentrations may lead to the penetration of salicylates from plasma into tissue and cause acetazolamide toxicity (fatigue, lethargy, drowsiness, confusion, hyperchloremic metabolic acidosis) and salicylate toxicity (vomiting, tachycardia, hyperpnea, confusion).
Probenecid, sulfinpyrazone. When probenecid and salicylates are used in high doses (500 mg), the metabolism of each other is inhibited and uric acid excretion may be reduced.
Combinations to be used with caution
Methotrexate. When using acetylsalicylic acid and methotrexate at doses of 15 mg/week, the hematological toxicity of methotrexate increases (reduction in renal clearance of methotrexate by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates).
Anticoagulants (warfarin, phenprocoumon). Thrombin production may be reduced, resulting in an indirect effect on platelet activity (vitamin K antagonist) and an increased risk of bleeding.
Abciximab, tirofiban, eptifibatide. Possible inhibition of glycoprotein IIb/IIIa receptors on platelets, leading to an increased risk of bleeding.
Heparin: There may be a decrease in thrombin production, resulting in an indirect effect on platelet activity, which leads to an increased risk of bleeding.
If two or more of the above substances are used together with acetylsalicylic acid, this may lead to a synergistic effect of increased inhibition of platelet activity and, as a result, to an increase in hemorrhagic diathesis.
NSAIDs and COX-2 inhibitors (celecoxib). Concomitant use increases the risk of gastrointestinal disorders, which may lead to gastrointestinal bleeding.
Ibuprofen. Concomitant use of ibuprofen inhibits irreversible platelet aggregation induced by acetylsalicylic acid. Treatment with ibuprofen in patients at increased risk of cardiovascular events may limit the cardioprotective effect of acetylsalicylic acid.
Patients who take acetylsalicylic acid once a day for the prevention of cardiovascular disease and occasionally take ibuprofen should take acetylsalicylic acid at least 2 hours before taking ibuprofen.
Furosemide: Inhibition of proximal tubular elimination of furosemide is possible, leading to a decrease in the diuretic effect of furosemide.
Quinidine: May have an additive effect on platelets, leading to increased bleeding time.
Spironolactone: Possible modified renin effect, leading to reduced efficacy of spironolactone.
Selective serotonin reuptake inhibitors: Concomitant use increases the risk of gastrointestinal disorders, which may lead to gastrointestinal bleeding.
Valproate. When used simultaneously with valproate, acetylsalicylic acid displaces it from its connection with blood plasma proteins, increasing the toxicity of the latter (suppression of CNS function, disorders of the gastrointestinal tract).
Systemic corticosteroids (excluding hydrocortisone, which is used for replacement therapy in Addison's disease) reduce the level of salicylates in the blood and increase the risk of overdose after the end of treatment.
Antidiabetic drugs. Concomitant use of acetylsalicylic acid and antidiabetic drugs increases the risk of hypoglycemia.
Antacids. Possible increase in renal clearance and decrease in renal absorption (due to increased urine pH), which leads to a decrease in the effect of acetylsalicylic acid.
Varicella vaccine. Concomitant use increases the risk of Reye's syndrome.
Ginkgo biloba. Concomitant use with ginkgo biloba inhibits platelet aggregation, which leads to an increased risk of bleeding.
Digoxin. When used simultaneously with digoxin, the concentration of the latter in the blood plasma increases due to a decrease in renal excretion.
Alcohol contributes to damage to the gastrointestinal mucosa and prolongs bleeding time due to the synergism of acetylsalicylic acid and alcohol.
Overdose
Toxicity.
Dangerous dose: Adults: 300 mg/kg body weight.
Chronic salicylate poisoning may be latent, as its signs and symptoms are nonspecific. Moderate chronic intoxication caused by salicylates, or salicylism, is usually observed only after repeated administration of the drug in high doses. Symptoms of moderate chronic poisoning (the result of prolonged use of the drug in high doses): dizziness, vertigo, deafness, increased sweating, fever, rapid breathing, tinnitus, respiratory alkalosis, metabolic acidosis, lethargy, moderate dehydration, headache, confusion, nausea and vomiting. Acute intoxication is evidenced by a pronounced change in the acid-base balance, which may differ depending on age and severity of intoxication. Metabolic acidosis is a frequent manifestation in children. The severity of the condition cannot be assessed solely on the basis of the concentration of salicylates in the blood plasma. Absorption of acetylsalicylic acid may be slowed down due to delayed gastric emptying, formation of stones in the stomach or when taking the drug in the form of enteric-coated tablets. Symptoms of severe and acute poisoning (due to overdose): hypoglycemia (mainly in children), encephalopathy, coma, arterial hypotension, pulmonary edema, convulsions, coagulopathy, cerebral edema, cardiac arrhythmias.
A more pronounced toxic effect occurs in patients with chronic overdose or abuse of the drug, as well as in the elderly or children.
Treatment. In case of acute overdose, gastric lavage and administration of activated charcoal are necessary. If a dose of more than 120 mg/kg of body weight is suspected, activated charcoal should be administered again.
Prothrombin time and/or international normalized ratio should be checked, particularly if bleeding is suspected.
It is necessary to restore the balance of fluids and electrolytes. Effective methods of removing salicylate from the blood plasma are alkaline diuresis and hemodialysis. Hemodialysis should be used in case of severe intoxication, since this method significantly accelerates the elimination of salicylates and restores the acid-base and water-salt balance.
Given the complex pathophysiological effects of salicylate poisoning, signs/symptoms/test results may include:
Manifestations and symptoms Test results Therapeutic measures
| lung intoxication or medium degree | | Gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis |
| Tachypnea, hyperventilation, respiratory alkalosis | Alkalemia, alkaluria | Restoration of electrolyte and acid-base balance |
| Diaphoresis (increased sweating) | | |
| Nausea and vomiting | | |
| intoxication of the middle or severe | | Gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis, hemodialysis in severe cases |
| Respiratory alkalosis with compensatory metabolic acidosis | Acidemia, aciduria | Restoration of electrolyte and acid-base balance |
| hyperpyrexia | | Restoration of electrolyte and acid-base balance |
| Respiratory: hyperventilation, noncardiogenic pulmonary edema, respiratory failure, asphyxia | | |
| Cardiovascular: dysrhythmias, hypotension, cardiovascular insufficiency | For example, changes in blood pressure, ECG | |
| Fluid and electrolyte loss: dehydration, oliguria, renal failure | For example, hypokalemia, hypernatremia, hyponatremia, altered renal function | Restoration of electrolyte and acid-base balance |
| metabolic disorder glucose, ketoacidosis | Hyperglycemia, hypoglycemia (especially in children). elevated level ketone bodies | |
| Ringing in the ears, deafness | | |
| Gastrointestinal: gastrointestinal bleeding | | |
| Hematological: platelet inhibition, coagulopathy | For example, prolonged prothrombin time, hypoprothrombinemia | |
| Neurological: toxic encephalopathy and CNS depression with manifestations such as lethargy, confusion, coma, seizures | | |
|
Storage conditions
At a temperature not exceeding 25 °C.
UA / TAK / 1218/0040
